4A49

Structure of phosphoTyr371-c-Cbl-UbcH5B complex

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d4a49b_	Alpha and beta proteins (a+b)	UBC-like	UBC-like	UBC-related	Ubiquitin conjugating enzyme, UBC	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	RING/U-box like	8039285	3000160	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	UBC-like	8040137	3000570	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF00097	e4a49A2	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: RING/U-box	F: PF00097	ECOD (1.6)
B	PF00179	e4a49B2	A: a+b two layers	X: UBC-like	H: UBC-like (From Topology)	T: UBC-like	F: PF00179	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.40.10	Alpha Beta	2-Layer Sandwich	Herpes Virus-1	Zinc/RING finger domain, C3HC4 (zinc finger)	CATH (4.3.0)
B	3.10.110.10	Alpha Beta	Roll	Ubiquitin Conjugating Enzyme	Ubiquitin Conjugating Enzyme	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00097	Zinc finger, C3HC4 type (RING finger) (zf-C3HC4)	Zinc finger, C3HC4 type (RING finger)	The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid [1]. Many protein ...	The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid [1]. Many proteins containing a RING finger play a key role in the ubiquitination pathway [2].	Domain
B	PF00179	Ubiquitin-conjugating enzyme (UQ_con)	Ubiquitin-conjugating enzyme	Proteins destined for proteasome-mediated degradation may be ubiquitinated. Ubiquitination follows conjugation of ubiquitin to a conserved cysteine residue of UBC homologues. TSG101 is one of several UBC homologues that lacks this active site cystein ...	Proteins destined for proteasome-mediated degradation may be ubiquitinated. Ubiquitination follows conjugation of ubiquitin to a conserved cysteine residue of UBC homologues. TSG101 is one of several UBC homologues that lacks this active site cysteine [4, 5].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	E3 ubiquitin-protein ligase CBL	phosphoprotein binding phosphotyrosine residue binding protein binding binding protein phosphorylated amino acid binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-like protein ligase activity ubiquitin protein ligase activity transferase activity catalytic activity ubiquitin-protein transferase activity phosphoprotein binding phosphotyrosine residue binding protein binding binding protein phosphorylated amino acid binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-like protein ligase activity ubiquitin protein ligase activity transferase activity catalytic activity ubiquitin-protein transferase activity SH3 domain binding protein domain specific binding cell adhesion molecule binding cadherin binding signaling receptor binding ephrin receptor binding protein tyrosine kinase binding kinase binding receptor tyrosine kinase binding enzyme binding protein kinase binding cation binding ion binding calcium ion binding metal ion binding small molecule binding phosphatidylinositol 3-kinase binding phosphatidylinositol 3-kinase regulatory subunit binding	cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process developmental process multicellular organismal process gonad development reproductive system development reproductive process sex differentiation animal organ development developmental process involved in reproduction cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process developmental process multicellular organismal process gonad development reproductive system development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics anatomical structure development reproductive structure development system development biological process involved in interspecies interaction between organisms entry of bacterium into host cell symbiont entry into host biological process involved in interaction with host biological process involved in symbiotic interaction response to organic substance regulation of biological process regulation of cellular process cell surface receptor signaling pathway signaling biological regulation response to cytokine cytokine-mediated signaling pathway cell communication cellular response to chemical stimulus response to chemical cellular response to cytokine stimulus cellular response to organic substance signal transduction response to ketone response to lipid response to oxygen-containing compound response to testosterone response to organic cyclic compound response to decreased oxygen levels cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus organonitrogen compound metabolic process protein autoubiquitination primary metabolic process organic substance metabolic process protein ubiquitination macromolecule modification metabolic process protein metabolic process macromolecule metabolic process post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal negative regulation of signaling negative regulation of ERBB signaling pathway negative regulation of biological process regulation of signal transduction cell surface receptor protein tyrosine kinase signaling pathway negative regulation of cell communication regulation of epidermal growth factor receptor signaling pathway negative regulation of cellular process epidermal growth factor receptor signaling pathway enzyme-linked receptor protein signaling pathway regulation of signaling regulation of ERBB signaling pathway negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus negative regulation of epidermal growth factor receptor signaling pathway ERBB signaling pathway regulation of cell communication positive regulation of cell communication positive regulation of signal transduction positive regulation of biological process positive regulation of response to stimulus positive regulation of ERBB signaling pathway positive regulation of cellular process positive regulation of epidermal growth factor receptor signaling pathway positive regulation of signaling cellular response to endogenous stimulus cellular response to growth factor stimulus response to endogenous stimulus cellular response to nerve growth factor stimulus response to nerve growth factor response to growth factor organonitrogen compound catabolic process catabolic process proteolysis involved in protein catabolic process protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process organic substance catabolic process protein polyubiquitination regulation of localization import into cell positive regulation of cellular component organization regulation of cellular component organization transport vesicle-mediated transport cellular component organization localization positive regulation of endocytosis cellular component organization or biogenesis positive regulation of receptor-mediated endocytosis regulation of endocytosis regulation of transport regulation of receptor-mediated endocytosis regulation of vesicle-mediated transport establishment of localization positive regulation of transport endocytosis receptor-mediated endocytosis platelet-derived growth factor receptor-alpha signaling pathway platelet-derived growth factor receptor signaling pathway regulation of platelet-derived growth factor receptor signaling pathway regulation of platelet-derived growth factor receptor-alpha signaling pathway protein monoubiquitination response to nutrient levels response to starvation cellular response to platelet-derived growth factor stimulus response to platelet-derived growth factor negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death response to activity small GTPase-mediated signal transduction regulation of small GTPase mediated signal transduction regulation of Rap protein signal transduction intracellular signal transduction regulation of intracellular signal transduction intracellular signaling cassette Rap protein signal transduction regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction protein localization ubiquitin-dependent endocytosis establishment of protein localization cellular localization nitrogen compound transport organic substance transport establishment of protein localization to organelle protein transport cellular macromolecule localization macromolecule localization protein localization to organelle response to alcohol response to ethanol establishment of organelle localization regulated exocytosis cell activation involved in immune response leukocyte degranulation myeloid leukocyte activation myeloid leukocyte mediated immunity leukocyte activation secretion by cell organelle localization leukocyte activation involved in immune response establishment of localization in cell mast cell activation leukocyte mediated immunity mast cell mediated immunity immune response secretion cell activation vacuolar localization export from cell mast cell degranulation myeloid cell activation involved in immune response immune effector process mast cell activation involved in immune response exocytosis immune system process lysosome localization response to ionizing radiation response to radiation response to gamma radiation	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane raft protein-containing complex plasma membrane protein complex plasma membrane raft membrane plasma membrane membrane protein complex caveola membrane microdomain cell periphery intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane raft protein-containing complex plasma membrane protein complex plasma membrane raft membrane plasma membrane membrane protein complex caveola membrane microdomain cell periphery flotillin complex plasma membrane region membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system perinuclear region of cytoplasm cell projection cilium plasma membrane bounded cell projection anchoring junction cell junction focal adhesion cell-substrate junction growth cone axon distal axon neuron projection site of polarized growth
B	Ubiquitin-conjugating enzyme E2 D2	binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding ubiquitin conjugating enzyme activity aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-like protein conjugating enzyme activity transferase activity catalytic activity ubiquitin-protein transferase activity ubiquitin protein ligase binding protein binding ubiquitin-like protein ligase binding enzyme binding ubiquitin-like protein ligase activity ubiquitin protein ligase activity	organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process organic substance metabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process metabolic process protein metabolic process organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process organic substance metabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process metabolic process protein metabolic process macromolecule metabolic process organic substance catabolic process protein polyubiquitination protein ubiquitination macromolecule modification post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal protein K48-linked ubiquitination protein autoubiquitination	extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol nucleus extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen nuclear lumen protein-containing complex ubiquitin ligase complex catalytic complex transferase complex intracellular protein-containing complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR024162	Adaptor protein Cbl	Family
A	IPR013083	Zinc finger, RING/FYVE/PHD-type	Homologous Superfamily
A	IPR009060	UBA-like superfamily	Homologous Superfamily
A	IPR001841	Zinc finger, RING-type	Domain
A	IPR036860	SH2 domain superfamily	Homologous Superfamily
A	IPR024159	Adaptor protein Cbl, PTB domain	Domain
A	IPR003153	Adaptor protein Cbl, N-terminal helical	Domain
A	IPR011992	EF-hand domain pair	Homologous Superfamily
A	IPR015940	Ubiquitin-associated domain	Domain
A	IPR018957	Zinc finger, C3HC4 RING-type	Domain
A	IPR017907	Zinc finger, RING-type, conserved site	Conserved Site
A	IPR014741	Adaptor protein Cbl, EF hand-like	Domain
A	IPR014742	Adaptor protein Cbl, SH2-like domain	Domain
A	IPR036537	Adaptor protein Cbl, N-terminal domain superfamily	Homologous Superfamily
B	IPR000608	Ubiquitin-conjugating enzyme E2	Domain
B	IPR016135	Ubiquitin-conjugating enzyme/RWD-like	Homologous Superfamily
B	IPR023313	Ubiquitin-conjugating enzyme, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P22681	juvenile myelomonocytic leukemia CBL-related disorder vasculitis male infertility cryptorchidism intellectual disability myelodysplastic syndrome ovarian cancer Abdominal Cryptorchidism primitive neuroectodermal tumor developmental disability glioblastoma hydrops fetalis pancreatic intraductal papillary-mucinous neoplasm acute myeloid leukemia juvenile myelomonocytic leukemia CBL-related disorder vasculitis male infertility cryptorchidism intellectual disability myelodysplastic syndrome ovarian cancer Abdominal Cryptorchidism primitive neuroectodermal tumor developmental disability glioblastoma hydrops fetalis pancreatic intraductal papillary-mucinous neoplasm acute myeloid leukemia rheumatoid arthritis cancer ulcerative colitis large cell medulloblastoma malignant glioma osteosarcoma Pick disease atypical teratoid rhabdoid tumor Sjogren syndrome congenital anemia genetic endocrine growth disease hematopoietic and lymphoid system neoplasm
B	Pharos: P62837	astrocytic tumor esophageal squamous cell carcinoma malignant ependymoma osteosarcoma atypical teratoid rhabdoid tumor glioblastoma malignant glioma ovarian cancer breast cancer large cell medulloblastoma malignant mesothelioma plasma cell myeloma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A	PTR	Parent Component: TYR RESID: AA0039 PSI-MOD : O4'-phospho-L-tyrosine MOD:00048

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.